MURAMYL DIPEPTIDE IMPROVES MONONUCLEAR PHAGOCYTE SYSTEM FUNCTION IN OBSTRUCTIVE-JAUNDICE

Previous studies have demonstrated depression of the mononuclear phagocyte system (MPS) of which the liver comprises 80-85% in animals subjected to 21 days of obstructive jaundice. This study examined the ability of a macrophage stimulant, muramyl dipeptide (MDP), to reverse MPS dysfunction in an obstructive jaundice rat model. Sixty-two male Sprague-Dawley rats underwent sham (n = 29) laparotomy or common duct ligation (CDL) (n = 33) and were studied after 21 days. Animals were injected with 1-3.5 × 106 Escherichia coli via a lateral tail vein, and colony-forming units (CFU) of the liver, lung, and spleen were determined at two time intervals: 30 min postinjection to determine the phagocytic activity of MPS (sham, n = 16; CDL, n = 20) and 24 hr postinjection to determine cytotoxic activity of MPS (sham, n = 13; CDL, n = 13). MDP (3 μg/g) was administered subcutaneously 24 hr prior to E. coli injection in 6 sham and 10 CDL rats studied at the 30-min time interval and 7 sham and 7 CDL rats studied at the 24-hr time interval. Pretreatment with MDP appeared to reverse the impairment of phagocytic activity in the liver of CDL rats returning it to the level of sham animals (P < 0.05). However, pretreatment with MDP did not enhance the cytotoxic activity of the MPS as evidenced by higher CFU of E. coli in the liver, lung, and spleen of CDL animals pretreated with MDP as compared to CDL animals that did not receive MDP pretreatment. This increase was only significant in the spleen. Therefore, we conclude that although initially pretreatment with an immunostimulant, MDP, reverses the phagocytic impairment of the liver in animals with obstructive jaundice, the cytotoxic abilities of MPS at 24 hr postinjection of E. coli are not enhanced by pretreatment with MDP. © 1990.